Aminoacyl tRNA synthetases for modulating inflammation

Abstract

Inflammatory and other cellular response-modulating compositions are provided comprising aminoacyl-tRNA synthetase polypeptides, including active fragments and/or variants thereof. Also provided are methods of using such compositions in the treatment of conditions that benefit from the modulation of inflammation, such as inflammatory diseases or conditions.

The invention claimed is: 
     
       1. A method for reducing inflammation of the respiratory system in a subject in need thereof, comprising administering to the subject a sterile composition, comprising a pharmaceutically-acceptable carrier and an isolated histidyl-tRNA synthetase (HRS) polypeptide selected from (a) a polypeptide that comprises SEQ ID NO:28, (b) a fragment of (a) comprising at least 400 contiguous amino acids of SEQ ID NO:28, and (c) a variant which differs from SEQ ID NO:28 by less than 10% of the residues of SEQ ID NO:28, wherein the HRS polypeptide has an anti-inflammatory activity and is at least about 90% pure. 
     
     
       2. The method of  claim 1 , wherein (b) is a fragment of SEQ ID NO:28 comprising at least 500 contiguous amino acids of SEQ ID NO:28. 
     
     
       3. The method of  claim 1 , wherein (c) is a variant which differs from SEQ ID NO:28 by less than 5% of the residues of SEQ ID NO:28. 
     
     
       4. The method of  claim 1 , wherein the subject in need thereof has inflammatory lung disease (ILD), acute respiratory distress syndrome (ARDS), or pneumonia. 
     
     
       5. The method of  claim 1 , wherein the subject in need thereof has fibrosis, sarcoidosis, rheumatoid arthritis, lupus erythematosus, polymyositis, dermatomyositis, graft vs. host disease, scleroderma, hypersensitivity, or microscopic polyangiitis. 
     
     
       6. The method of  claim 1 , wherein the subject in need thereof has a condition selected from atopic asthma, non-atopic asthma, allergic asthma, atopic bronchial IgE-mediated asthma, bronchial asthma, essential asthma, true asthma, intrinsic asthma caused by pathophysiologic disturbances, extrinsic asthma caused by environmental factors, essential asthma of unknown or inapparent cause, non-atopic asthma, bronchitic asthma, emphysematous asthma, exercise-induced asthma, allergen induced asthma, cold air induced asthma, occupational asthma, infective asthma caused by bacterial, fungal, protozoal, or viral infection, non-allergic asthma, incipient asthma, wheezy infant syndrome and bronchiolytis, chronic or acute bronchoconstriction, chronic bronchitis, small airways obstruction, or emphysema. 
     
     
       7. The method of  claim 1 , wherein the subject in need thereof has an obstructive or inflammatory airway disease. 
     
     
       8. The method of  claim 7 , wherein the obstructive or inflammatory airways disease is chronic eosinophilic pneumonia, chronic obstructive pulmonary disease (COPD), COPD that includes chronic bronchitis, pulmonary emphysema or dyspnea associated or not associated with COPD, COPD that is characterized by irreversible, progressive airways obstruction, or adult respiratory distress syndrome (ARDS). 
     
     
       9. The method of  claim 1 , wherein the subject in need thereof has a condition related to exacerbation of airways hyper-reactivity consequent to other drug therapy, airway disease that is associated with pulmonary hypertension, bronchitis or acute bronchitis, acute laryngotracheal bronchitis, arachidic bronchitis, catarrhal bronchitis, croupus bronchitis, dry bronchitis, infectious asthmatic bronchitis, productive bronchitis, staphylococcus or streptococcal bronchitis, vesicular bronchitis, acute lung injury, bronchiectasis or cylindric bronchiectasis, sacculated bronchiectasis, fusiform bronchiectasis, capillary bronchiectasis, cystic bronchiectasis, dry bronchiectasis, or follicular bronchiectasis. 
     
     
       10. The method of  claim 1 , for desensitizing immune cells to self antigens, foreign antigens, irritants, allergens, or infectious agents related to pulmonary inflammation. 
     
     
       11. The method of  claim 1 , which is utilized in combination with a treatment for pulmonary inflammation, selected from lung rehabilitation; the use of bronchodilators, steroids or corticosteroids, antibiotics, metered-dose inhalers (MDIs), dry powder inhalers (DPIs), nebulizers, or oxygen therapy; and surgery, optionally bullectomy, lung volume reduction surgery, or lung transplant. 
     
     
       12. The method of  claim 11 , wherein the bronchodilators are selected from ipratropium, tiotropium, salmeterol, and formoterol.